Uteroferrin and recombinant bovine GM-CSF modulate the myelosuppressive effects of 5-fluorouracil in young female pigs (Sus scrofa).
The present study investigated the ability of uteroferrin and recombinant bovine granulocyte monocyte/macrophage-colony stimulating factor (rbGM-CSF) to modulate the myelosuppressive effects of 5-fluorouracil (5-FU) in young female pigs (Sus scrofa). Pigs (N = 3/treatment) were infused with 5-FU (32.5 mg/kg) on days 0 and 1 of the experimental period. Uteroferrin (100 micrograms/kg in 0.9% NaCl), rbGM-CSF (10 micrograms/kg in 0.9% NaCl), uteroferrin + rbGM-CSF (as above) or control (0.9% NaCl) were administered as intramuscular injections twice daily (0800 and 2000 hr). Peripheral blood cell number, composition, and progenitor cells were determined over 28 days. Treatment of pigs with 5-FU resulted in a rapid leukocytopenia and thrombocytopenia (nadirs on days 5 and 7, respectively) and a modest decrease (P < 0.05) in red blood cell (RBC) number (nadir on day 14). Although nor affecting RBC and thrombocytes, treatment of pigs with uteroferrin had an initial protective effect (P < 0.05) on the 5-FU-induced leukocytopenia (63 and 64 vs 48 and 39 +/- 6% of baseline on days 3 and 5, respectively). In contrast, rbGM-CSF enhanced (P < 0.05) the rate of the leukocytopenia and had only minor effects on thrombocyte numbers relative to controls. These effects appeared to be additive, as pigs treated with uteroferrin + rbGM-CSF had a reduced rate of leukocytopenia compared to pigs treated with rbGM-CSF alone. Uteroferrin + rbGM-CSF also attenuated (P < 0.05) the suppression and enhanced (P < 0.05) recovery of RBC and thrombocyte numbers following 5-FU treatment. In control pigs, a modest rebound leukocytosis (122 +/- 6% of baseline) and thrombocytosis (141 +/- 9% of baseline) was evident. Uteroferrin enhanced (P < 0.05) the rebound leukocytosis (135 +/- 6% of baseline), but attenuated (P < 0.05) the thrombocytosis. In contrast, rbGM-CSF enhanced (P < 0.05) the duration of the leukocytosis during the recovery phase, an effect augmented by the combination of uteroferrin + rbGM-CSF. In addition, treatment with uteroferrin + rbGM-CSF resulted in a sustained thrombocytosis (days 12 to 21). As indicated by changes in CFU-GM, BFU-E, and CFU-GEMM progenitor cells in peripheral blood, the effects of uteroferrin and rbGM-CSF appeared to reflect their ability to enhance the proliferation and/or differentiation of both similar and distinct hematopoietic progenitor cells.
Laurenz
J C
JC
Department of Animal Science, Texas A&M University, College Station 77843-2471, USA.
Hadjisavas
M
M
Schuster
D
D
Bazer
F W
FW
D000135:Acid Phosphatase; D000367:Age Factors; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002417:Cattle; D003114:Colony-Forming Units Assay; D004906:Erythrocyte Count / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007527:Isoenzymes; D007962:Leukocytes / Q000187:drug effects*; D008667:Metalloproteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase
D007527:Isoenzymes; D008667:Metalloproteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D005472:Fluorouracil